Grant: Team Grant: Vision, Hearing and Communication Disorders - LOI

Cell death by apoptosis is the final common pathway for many forms of retinal disease, including glaucoma, retinitis pigmentosa, retinal ischemia, age-related macular degeneration and diabetic retinopathy. As such, any gene therapy strategy which targets the apoptotic cascade could potentially be applicable to many different types of retinal degeneration. Apoptosis of the cell occurs through the action of a family of proteins called caspases. The IAP (inhibitor of apoptosis) family of proteins has been shown to bind with and block the action of caspases. Our research examines the efficacy of using XIAP (X-linked IAP) to prevent apoptosis in several forms of retinal degeneration. XIAP has been shown to interact with and inhibit the action of several caspases. It has previously been shown that XIAP provides a significant degree of protection in animal models of neurodegenerative disease such as stroke, Parkinson's and Huntington's disease. We have shown that XIAP can prevent cell death in animal models of retinal ischemia, retinal detachment and in genetic forms of retinitis pigmentosa (RP). We believe that these studies provide significant proof-of-principle for XIAP efficacy in the treatment of human retinal disease. The current proposal will help to establish a multidisciplinary team of basic and clinical scientists that will help to translate the basic science results and data into the clinic. We will optimize gene therapy delivery parameters in larger animals, assess safety and efficacy issues associated with viral delivery of XIAP to the eye and develop strategies for the rapid targeting of XIAP to the eye. By the end of the five-year granting period, we will develop the technology so as to be in a position to initiate human clinical trials.